Novel Adenosine-Derived Inhibitors of 70 kDa Heat Shock Protein, Discovered Through Structure-Based Design
Year: 2009
Type: article
Abstract: The design and synthesis of novel adenosine-derived inhibitors of HSP70, guided by modeling and X-ray crystallographic structures of these compounds in complex with HSC70/BAG-1, is described. Examples exhibited submicromolar affinity for HSP70, were highly selective over HSP90, and some displayed potency against HCT116 cells. Exposure of compound 12 to HCT116 cells caused significant reduction in cellular levels of Raf-1 and Her2 at concentrations similar to that which caused cell growth arrest.
Source: Journal of Medicinal Chemistry
DOI: 10.1021/jm801627a
Authors: Douglas S. Williamson, Jenifer Borgognoni, Alexandra Clay, Zoe Daniels, Pawel Dokurno, Martin J. Drysdale, Nicolas Foloppe, Geraint L. Francis, Christopher J. Graham, Rob Howes, Alba T. Macias, James B. Murray, Rachel Parsons, Terry Shaw, Allan E. Surgenor, Lindsey Terry, Yikang Wang, Mike Wood, Andrew J. Massey
Institution: Vernalis (R&D) Limited (United Kingdom)
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2005459694